L-Asparagine (ASN) is the catalyze substrate of L-asparaginase (ASNase), which is an important drug for acute lymphoblastic leukemia (ALL) patients. The ASN level is found to be closely associated with the effectiveness of ASNase treatment. In this study, a hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method was developed for the determination of ASN in the human serum using a stable isotope-labeled internal standard (ASN-D3). Serum samples were prepared by a one-step precipitation procedure using methanol and separated by an Agilent HILIC Plus column with the mobile phase of methanol-water (95??5, v/v, containing 5?mM ammonium formate and 0.1% formic acid), at a constant flow rate of 0.3?mL/min. Mass spectrometric analysis was conducted using multiple-reaction monitoring in the positive electrospray ionization mode. Serum ASN concentrations were determined over a linear calibration curve range of 2-200?μM, with acceptable accuracies and precisions. The validated HILIC-MS/MS method was successfully applied to the quantification of ASN levels in the serum from patients with ALL. Collectively, the research may shed new light on an alternative rapid, simple, and convenient quantitative method for determination of serum ASN in ALL patients treated with ASNase. Copyright © 2020 Haoyang Lu et al.Dysplastic nevi (DN) are common and controversial and the best choice for management of DN after diagnosis is not always clear. The presence of positive margins found on diagnostic biopsy is used by many dermatologists when deciding whether to re-excise these lesions. In order to quantify the predictive value of positive margins in diagnostic biopsies of DN, we performed a review and analysis of the concordance between the histological findings of biopsies and their subsequent excisions. A total of 122 pathology reports from diagnostic biopsies of DN with nevus cells present at the tissue margin were reviewed. Within this sample, 68 total postbiopsy excisions had been performed. The excisional pathology reports were reviewed for the presence of residual or recurrent nevus cells. Residual nevus cells were reported in 29 of 63 available excisional pathology reports illustrating a positive predictive value (PPV) of positive margins in diagnostic biopsies of DN of 46.0%. We present this value along with PPVs from the very few existing similar studies. The quantified predictive value of positive margins in diagnostic biopsies is useful information for providers who must make decisions regarding the best treatment options for patients with DN. The low PPV of positive margins lends further evidence that DN of moderate severity or less may simply be monitored. Copyright © 2020 Jeffrey S. Dickman et al.Background Cancer is the second most common fatal disease in the world, behind cardiovascular disorders in the first place. It accounts for around 0.3 million deaths per year in India due to the lack of proper diagnostic facilities, prevention and treatment. Current therapeutic methods do not provide adequate protection and affect normal cells along with cancerous ones. Thus, there is a need for some alternative therapeutic strategy, preferably from natural products, which have been traditionally used for treatment of various diseases in the country. Methods In this study, we have conjugated purified NN-32 toxin from Naja naja venom with gold nanoparticles and its anticancer potential was evaluated against human breast cancer cell lines. UV-Vis spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy and zeta potential analysis were the techniques used for characterization of GNP-NN-32. Results GNP-NN-32 showed dose- and time-dependent cytotoxicity against breast cancer cell lines (MCF-7 and MDA-MB-231). NN-32 and GNP-NN-32 induced apoptosis in both breast cancer cell lines. The results of CFSE cell proliferation study revealed that NN-32 and GNP-NN-32 arrested cell division in both MCF-7 and MDA-MB-231 cell lines resulting in inhibition of proliferation of these cancer cells. Conclusion GNP-NN-32 showed an anticancer potential against human breast cancer cell lines. Analysis of detailed chemical characterization along with its cytotoxic property might help to perceive a new dimension of the anti-cancer potential of GNP-NN-32 that will enhance its biomedical function in near future.MicroRNA (miRNA)-gene interactions are well-recognized as involved in the progression of almost all cancer types including prostate cancer, which is one of the most common cancers in men. This study explored the significantly dysregulated genes and miRNAs and elucidated the potential miRNA-gene regulatory network in prostate cancer. Integrative analysis of prostate cancer and normal prostate transcriptomic data in The Cancer Genome Atlas dataset was conducted using both differential expression analysis and weighted correlation network analysis (WGCNA). Thirteen genes (RRM2, ORC6, CDC45, CDKN2A, E2F2, MYBL2, CCNB2, PLK1, FOXM1, CDC25C, PKMYT1, GTSE1, and CDC20) were potentially correlated with prostate cancer based on functional enrichment analyses. MiRNAs targeting these genes were predicted and eight miRNAs were intersections between those miRNAs and the hub miRNAs obtained from miRNA WGCNA analysis. https://www.selleckchem.com/ Three genes (E2F2, RRM2, and PKMYT1) and four miRNAs (hsa-mir-17-5p, hsa-mir-20a-5p, hsa-mir-92a-3p, and hsa-mir-93-5p) were key factors according to the interaction network. RRM2 and PKMYT1 were significantly related to survival. These findings partially elucidated the dysregulation of gene expressions in prostate cancer. Efficient manipulations of the miRNA-gene interactions in prostate cancer may be exploited as promising therapeutics. Copyright © 2020 Wei, Yin, Deng, Zhou, Wang, Yin, Yang and Tang.Several recent studies have demonstrated the utility of RNA-Seq in the diagnosis of rare inherited disease. Diagnostic rates 35% higher than those previously achievable with DNA-Seq alone have been attained. These studies have primarily profiled gene expression and splicing defects, however, some have also shown that fusion transcripts are diagnostic or phenotypically relevant in patients with constitutional disorders. Fusion transcripts have traditionally been studied as oncogenic phenomena, with relevance only to cancer testing. Consequently, fusion detection algorithms were biased toward the detection of well-known oncogenic fusions, hindering their application to rare Mendelian genetic disease studies. A recent methodology published by the authors successfully tailored a traditional algorithm to the detection of pathogenic fusion events in inherited disease. A key mechanism of decreasing false positive or biologically benign events was comparison to a database of events detected in normal tissues. This approach is akin to population frequency-based filtering of genetic variants.